Tissue Phantoms Research Articles

Monte Carlo study of nanoparticles effectiveness on the dose enhancement when irradiated by protons

Recently, the nanomedicine field has experienced considerable growth in research. The use of nanoparticles to enhance dose in radiation treatment was proposed and their potential effects can be indicated using Monte Carlo calculations. The main goal of this study focused on nanoparticles’ (NPs) effects on dose enhancement due to the low-energy protons because the majority of studies on NPs have been conducted for photon radiations. To investigate the effect of NPs on the Dose Enhancement Factor (DEF), a cell dimension phantom was modeled and spheres of NPs were localized inside that. Different NPs, such as Au, Pt, Ag, I, and Ta2O3, were located in the phantom, and the DEF was calculated by changing the source energy from 3 to 15 MeV. The purpose of investigating the low-energy proton beam is to clarify the effects around the Bragg peak in the presence of nanoparticles. For protons with an energy range of 3–15 MeV, it was discovered that Pt nanoparticles have a greater dose increase coefficient of about 1.8 times compared to the other nanoparticles. The findings indicated that the DEF values substantially depended on the NPs concentration, but that the DEF was not significantly affected by changes in concentration or nanoparticle size. Comparative calculations between water and soft tissue phantoms that were filled with NPs presented a difference of less than 2%. The obtained findings emphasized the importance of NPs and considered details, such as concentration, to demonstrate the potential of nanoparticles in improving treatment using protons.

Holography-based measurement of sound speed and attenuation coefficient values for small samples of tissue phantoms

For therapeutic ultrasound applications, design and planning of treatments often involve simulations to predict the in situ acoustic field, and these simulations rely on estimates of the acoustic properties of soft tissues. As defined in simulation models, these properties describe how a plane wave propagates in a homogeneous medium. However, because soft tissues inherently contain inhomogeneities, measurements are most appropriately performed on small, relatively homogeneous samples. In addition, mostly small samples of human tissue, either autopsy or post-surgical, are typically available for characterization. As published in a recent paper [J. Acoust. Soc. Am. 2021, 149(1): 386–404], we have proposed a holography-based technique to extract plane-wave measurements from ultrasound beams passing through small (cm-sized) material samples. Here, we seek to adapt this technique for measuring small samples of deformable materials using an apparatus that holds such samples with two plane, parallel surfaces that can be interrogated by an incident ultrasound beam having a diameter smaller than that of the sample. Initial testing over a range of frequencies from 0.5 to 10MHz is performed utilizing well characterized materials, such as hydrogels and silicone rubber. [Work supported by NIH grant R01EB025187.]

3D printable phantom for mimicking electrical properties of dermal tissue.

Skin cancer is one of the most ubiquitous forms of cancer that is often overdiagnosed or missed by traditional diagnostic techniques. Bioimpedance spectroscopy (BIS) is a technology that aims to take advantage of the variations in electrical properties of tissue to identify ectopic formations. It is difficult to develop BIS technologies without obtaining tumor tissue samples. One solution is to use a "tissue phantom," a synthetic structure that mimics the properties of tissue. Current solutions using natural biomaterials, such as gelatin, have not been able to create complex tissue geometries that are vital to honing BIS diagnostics. However, semi-synthetic polymers, such has gelatin methacrylate (GelMA), offer the benefits of possessing similar electrical properties to their respective source biomaterial while being 3D printable. In this work, we first measured the impedance of porcine dermal tissue. We then applied these impedance measurements to create an electrically accurate tissue phantom using a photocurable hydrogel, GelMA, and varying concentrations of NaCl, aluminum powder, and titanium dioxide powder.

QUANTITATIVE ANALYSIS OF ELECTRICAL CURRENT EFFECT ON MAGNETIC RESONANCE IMAGE TISSUE INTENSITY

Recent studies in magnetic resonance imaging (MRI) aim to improve image quality while reducing scan time. Electrical current injection in the form of magnetic resonance electrical impedance tomography (MREIT) is believed to be affecting image quality and scan time thus can improve the possibility of becoming a non-chemical contrast agent in MRI. This study will observe and analyze the effect of electrical current injection on a phantom object to determine whether there is a different tissue image intensity. A thigh of lamb was used as a biological tissue phantom. The scan was performed on both T1and T2-weighted without and with an electrical current injection of 0.5 mA Electrical current injection decreased mean of tissue image intensity on T1-weighted images on both muscle (1759 vs 794) and bone (2752 vs 1550) (p<0.05). On the other hand, the electrical current increased mean of tissue image intensity on T2-weighted images on both muscle (303 vs 897) and bone (579 vs 1499) (p<0.05). There is also a difference in tissue image intensity on both T1 and T2-weighted images with and without electrical current injection on bone and muscle. The implication of this difference in image quality is a subject for further study.

Development of a platform for broadband, spectra-fitted, tissue optical phantoms.

Current methods of producing optical phantoms are incapable of accurately capturing the wavelength-dependent properties of tissue critical for many optical modalities. We aim to introduce a method of producing solid, inorganic phantoms whose wavelength-dependent optical properties can be matched to those of tissue over the wavelength range of 370 to 950nm. The concentration-dependent optical properties of 20 pigments were characterized and used to determine combinations that result in optimal fits compared to the target properties over the full spectrum. Phantoms matching the optical properties of muscle and nerve, the diffuse reflectance of pale and melanistic skin, and the chromophore concentrations of a computational skin model with varying oxygen saturation ( ) were made with this method. Both optical property phantoms were found to accurately mimic their respective tissues' absorption and scattering properties across the entire spectrum. The diffuse reflectance phantoms were able to closely approximate skin reflectance regardless of skin type. All three computational skin phantoms were found to have emulated chromophore concentrations close to the model, with an average percent error for the of 4.31%. This multipigment phantom platform represents a powerful tool for creating spectrally accurate tissue phantoms, which should increase the availability of standards for many optical techniques.

MR elastography of soft porous tissue phantoms with varying macrostructure and pore pressure

Tissue porosity pressure mechanics play a vital role in the physiological workings and anatomical structures of soft tissue. Further understanding relationships between the pressurized state of the tissue and its function by noninvasive measurements may lead to new diagnostic methods for identifying early stages of disease pathology. The purpose of this study was to investigate the ability of Magnetic Resonance Elastography (MRE) to identify mechanics related to different pressurized states of porous soft tissue-like media. Phantoms with variations in stiffness and porous network geometries are scanned with MRE at 9.4 Tesla while pore pressure is quasi-statically loaded with 0, 50, 100, 150 mmHg gauge using air and liquid pressure. The MRE-derived shear modulus of tissue around isolated pores correlates with pore pressure. However, this was not observed for interconnected porous systems, in which the shear wavelength is much larger than the distance between neighboring pore branches. In these systems, the presented experimental results highlight the importance of a compressibility marker derived from 3D MRE acquisitions, which may be sensitive to pore pressure and pore network geometry.

Application of state equations approach to solve the classical Kubelka-Munk differential equations in turbid environment

The Kubelka-Munk (KM) model is frequently used to describe the optical properties (absorption and scattering) of inhomogeneous media in terms of the measured reflection and transmittance. The classical KM is modeled by two fluxes which counterpropagate in the media and can be described by system of differential equations. This system, on the other hand, can also be rewritten in the form of state equations, widely used in many areas of engineering such as electrical circuits, control systems and more. Here, we describe the simple mathematical expression of light reflectance and transmittance in turbid media based on the KM light propagation model via a system of state equations. To this end, we demonstrate the use of the state equations to solve KM differential equations in a simple and straightforward manner. To validate the solution of our model against the KM solution, different turbid media including tissue phantoms, milk with varying concentrations of sugar, human hands, and mouse brain were tested. We used a spatial frequency domain imaging system to recover the absorption and scattering properties of each of the media. These measured properties were then introduced into both models to obtain diffuse light reflectance and transmittance information. Experimental results demonstrate significant concurrence between the two approaches within a minute difference in all tested cases. The results presented in this study demonstrate the validity of our alternative strategy to the traditional KM solution.

Quantitative monitoring and modelling of retrodialysis drug delivery in a brain phantom

A vast number of drug molecules are unable to cross the blood-brain barrier, which results in a loss of therapeutic opportunities when these molecules are administered by intravenous infusion. To circumvent the blood-brain barrier, local drug delivery devices have been developed over the past few decades such as reverse microdialysis. Reverse microdialysis (or retrodialysis) offers many advantages, such as a lack of net volume influx to the intracranial cavity and the ability to sample the tumour’s micro-environment. However, the translation of this technique to efficient drug delivery has not been systematically studied. In this work, we present an experimental platform to evaluate the performance of microdialysis devices in reverse mode in a brain tissue phantom. The mass of model drug delivered is measured by computing absorbance fields from optical images. Concentration maps are reconstructed using a modern and open-source implementation of the inverse Abel transform. To illustrate our method, we assess the capability of a commercial probe in delivering methylene blue to a gel phantom. We find that the delivery rate can be described by classical microdialysis theory, except at low dialysate flow rates where it is impacted by gravity, and high flow rates where significant convection to the gel occurs. We also show that the flow rate has an important impact not only on the overall size of the drug plume, but also on its shape. The numerical tools developed for this study have been made freely available to ensure that the method presented can be used to rapidly and inexpensively optimise probe design and protocol parameters before proceeding to more in-depth studies.

Better phasor calibration in turbid media using Monte Carlo simulations.

Phasor analysis has gained acceptance as a simpler yet quantitative alternative to nonlinear fitting approaches for in vitro fluorescence lifetime imaging microscopy (FLIM) and is incorporated into many commercial and research analysis software. FLIM typically involves cell monolayers, thin tissue slices or transparent spheroids, which do not introduce significant light scattering or absorption effects. As a result, the recorded fluorescence decay is a mere convolution product of the instrument response function and the emitted decay. However, the situation is more complex when in tissue phantoms or live animals observed with macroscopic fluorescence lifetime imaging (MFLI) systems, where those effects become noticeable. In particular, when using the phasor approach to analyze MFLI data, they result in an inadequacy to properly calibrate the phasor of measured decays using the simple approach used in FLIM. Namely, a discrepancy between observed calibrated phasor locations and those expected is generally observed in the simple cases where single-exponential decays are known to occur, no matter what calibration approach is used. This calls for a way to take these effects into account to obtain more quantitative results in this general situation of fluorescence in turbid media.

Data-Driven Steering of Concentric Tube Robots in Unknown Environments via Dynamic Mode Decomposition

Concentric Tube Robots (CTRs) are a type of continuum robot capable of manipulating objects in restricted spaces and following smooth trajectories. CTRs are ideal instruments for minimally invasive surgeries. Accurate control of CTR's motion in presence of contact with tissue and external forces will allow safe deployment of the robot in a variety of minimally invasive surgeries. Here, we propose a data-driven controller that can repeatedly and precisely direct the robot along predetermined deployment trajectories. The proposed controller doesn't rely on a mathematical model of the robot and employs Extended Dynamic Mode Decomposition (EDMD) to learn the nonlinear dynamics of the robot and the interaction forces on the fly. This enables the robot to follow desired trajectories in the presence of unknown perturbations, such as external forces. Experiments are carried out to evaluate the accuracy of the controller in steering the robot on arbitrary trajectories. Results demonstrate that the robot can track trajectories with a mean accuracy of 2.4 mm in repeated trials. Furthermore, we simulate scenarios where the robot is in contact with a rigid obstacle and is cutting through phantom tissue. Results show the robot can reach various static targets with a minimum accuracy of 2 mm.

Complex Correlated Phase Gradient Variance Based Optical Coherence Tomography Angiography

In this study, we reported a complex-signal-based optical coherence tomography angiography (OCTA) method, called complex correlated phase gradient variance (CCPGV), for mapping high-quality microvascular images. The performance of the newly proposed algorithm is benchmarked against the previously reported phase-resolved Doppler variance, complex differential variance (CDV), and split-spectrum amplitude and phase-gradient angiography (SSAPGA), by both tissue phantoms experiments and in vivo human skin measurements. Compared to the phase-resolved Doppler variance, CCPGV can intrinsically reject undesirable phase shifts caused by bulk motion and trigger jitter. In contrast to CDV and SSAPGA, which are insensitive to phase instability, CCPGV can provide superior motion contrast, as demonstrated by ∼1.4 and 3 times higher contrast in phantom experiments respectively. An increase of 27.3% and 106.3% were found in vivo experiments for CCPGV, making it easier to distinguish vessels from the background static. Benefiting from the advantages, more vessels and better connectivity can be visualized in the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">en</i> -face angiogram processed by the CCPGV method. We believe that our method will benefit the biomedical community to some extent in disease diagnosis and monitoring.

Engineering Tridimensional Hydrogel Tissue and Organ Phantoms with Tunable Springiness

AbstractBiomimicking organ phantoms with vivid biological structures and soft and slippery features are essential for in vitro biomedical applications yet remain hither to unmet challenges in their fabrication such as balancing between spatial structural complexity and matchable mechanical properties. Herein, 3D printable tissue‐mimicking elastomeric double network hydrogels with tailorable stiffness are evolved to idiosyncratically match diverse biological soft tissues by regulating the compositions of hydrogel matrix and the density of metal coordination bonds. Relying on digital light processing 3D printing, various mechanically tunable biomimetic volumetric hydrogel organ constructs with structural complexity and fidelity, including kidney, brain, heart, liver, stomach, lung, trachea, intestine, and even the intricate vascularized tissues, are fabricated faultlessly. Proof‐of‐concept 3D printed hydrogel heart and liver phantoms provide sophisticated internal channels and cavity structures and external realistic anatomical architectures that more closely mimic native organs. For the in vitro application demonstration, a 3D printed hydrogel brain phantom with tortuous cerebral arteries and slippery characters serves as an effective neurosurgical training platform for realistic simulation of endovascular interventions. This platform offers a means to construct mechanically precisely tunable hydrogel‐based biomimetic organ phantoms that are expected to be used in surgical training, medical device testing, and organs‐on‐chips.

Using Ultrasound Image Augmentation and Ensemble Predictions to Prevent Machine-Learning Model Overfitting.

Deep learning predictive models have the potential to simplify and automate medical imaging diagnostics by lowering the skill threshold for image interpretation. However, this requires predictive models that are generalized to handle subject variability as seen clinically. Here, we highlight methods to improve test accuracy of an image classifier model for shrapnel identification using tissue phantom image sets. Using a previously developed image classifier neural network-termed ShrapML-blind test accuracy was less than 70% and was variable depending on the training/test data setup, as determined by a leave one subject out (LOSO) holdout methodology. Introduction of affine transformations for image augmentation or MixUp methodologies to generate additional training sets improved model performance and overall accuracy improved to 75%. Further improvements were made by aggregating predictions across five LOSO holdouts. This was done by bagging confidences or predictions from all LOSOs or the top-3 LOSO confidence models for each image prediction. Top-3 LOSO confidence bagging performed best, with test accuracy improved to greater than 85% accuracy for two different blind tissue phantoms. This was confirmed by gradient-weighted class activation mapping to highlight that the image classifier was tracking shrapnel in the image sets. Overall, data augmentation and ensemble prediction approaches were suitable for creating more generalized predictive models for ultrasound image analysis, a critical step for real-time diagnostic deployment.

Light distribution in fat cell layers at physiological temperatures

Adipose tissue (AT) optical properties for physiological temperatures and in vivo conditions are still insufficiently studied. The AT is composed mainly of packed cells close to spherical shape. It is a possible reason that AT demonstrates a very complicated spatial structure of reflected or transmitted light. It was shown with a cellular tissue phantom, is split into a fan of narrow tracks, originating from the insertion point and representing filament-like light distribution. The development of suitable approaches for describing light propagation in a AT is urgently needed. A mathematical model of the propagation of light through the layers of fat cells is proposed. It has been shown that the sharp local focusing of optical radiation (light localized near the shadow surface of the cells) and its cleavage by coupling whispering gallery modes depends on the optical thickness of the cell layer. The optical coherence tomography numerical simulation and experimental studies results demonstrate the importance of sharp local focusing in AT for understanding its optical properties for physiological conditions and at AT heating.

Assessing reliability and validity of different stiffness measurement tools on a multi-layered phantom tissue model

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools’ (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75–0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.

Evaluating the Use of Surface Plasmon Resonance-Based Sensing for Colorectal Mucosa Cancer Detection

This paper presents an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in silico</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</i> study concerning the application of a trapezoidal prism-based surface plasmon resonance chip to detect colorectal cancer by analyzing the mucosa tissue. The sensor is a multilayered structure and works in the wavelength interrogation mode. Performance parameters related to the metallic film characteristics, such as thickness and type of metal were determined. For the analyzed noble metals, the silver film of 40 nm has the highest sensitivity of 6,454.12 nm/RIU, and the 60 nm-thick presents the best values for full width at half maximum and χ parameter (20.20 nm and 286.63 RIU <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">–1</sup> ). The palladium nanolayer deposition enhanced the sensitivity by 10.81% for copper film and peaks at 6,497.04 nm/RIU for the silver film. The palladium nanolayer also provokes deeper dips in the reflectance spectrum. Tissue phantoms were used to study the sensor response to solid surrounding medium to show the feasibility and the correctness of the proposed methodology.

Shear wave generation from non-spherical bubble collapse in a tissue phantom.

Elastography is a non-invasive technique to detect tissue anomalies via the local elastic modulus using shear waves. Commonly shear waves are produced via acoustic focusing or the use of mechanical external sources, shear waves may result also naturally from cavitation bubbles during medical intervention, for example from thermal ablation. Here, we measure the shear wave emitted from a well-controlled single laser-induced cavitation bubble oscillating near a rigid boundary. The bubbles are generated in a transparent tissue-mimicking hydrogel embedded with tracer particles. High-speed imaging of the tracer particles and the bubble shape allow quantifying the shear wave and relate it to the bubble dynamics. It is found that different stages of the bubble dynamics contribute to the shear wave generation and the mechanism of shear wave emission, its direction and the efficiency of energy converted into the shear wave depend crucially on the bubble to wall stand-off distance.

In Situ Measurement of Intra-tumoral Tissue Rigidity.

Local tissue scale mechanical properties are essential for understanding cell fate and function; however, few methods to measure stiffness at this length scale exist, and applications in 3D tissues can present further challenges. To address this need, microgel-based sensors fabricated out of the thermally responsive hydrogel poly(N-isopropylacrylamide) were developed allowing internal architectures of tissues to be mapped by optically measuring microgel response when actuated in a matrix. These robust probes are widely applicable for in vitro and in vivo studies of tissue mechanics providing tissues can be fluorescently imaged. Here we describe the fabrication of these thermally responsive hydrogel sensors, calibration of the microgels using phantom tissues, and image processing techniques used to make the measurements.

Tissue-Mimicking Materials for Ultrasound-Guided Needle Intervention Phantoms: A Comprehensive Review.

Ultrasound-guided needle interventions are common procedures in medicine, and tissue-mimicking phantoms are widely used for simulation training to bridge the gap between theory and clinical practice in a controlled environment. This review assesses tissue-mimicking materials from 24 studies as candidates for a high-fidelity ultrasound phantom, including methods for evaluating relevant acoustic and mechanical properties and to what extent the reported materials mimic the superficial layers of biological tissue. Speed of sound, acoustic attenuation, Young's modulus, hardness, needle interaction forces, training efficiency and material limitations were systematically evaluated. Although gelatin and agar have the closest acoustic values to tissue, mechanical properties are limited, and strict storage protocols must be employed to counteract dehydration and microbial growth. Polyvinyl chloride (PVC) has superior mechanical properties and is a suitable alternative if durability is desired and some ultrasound realism to human tissue may be sacrificed. Polyvinyl alcohol (PVA), while also requiring hydration, performs well across all categories. Furthermore, we propose a framework for the evaluation of future ultrasound-guided needle intervention tissue phantoms to increase the fidelity of training programs and thereby improve clinical performance.

Selective plane illumination optical endomicroscopy with polymer imaging fibers

Imaging fibers are used to perform real-time fluorescence endomicroscopy, in vivo, in situ, with the goal of increasing diagnostic information for a plethora of organ systems and diseases. Widefield fiber endomicroscopy systems are simple, cost-effective, and come with fast image acquisition times. However, alternative approaches such as scanning systems produce higher contrast images with intrinsic optical sectioning, improving the visibility of histological features, albeit at the expense of simplicity, cost, and acquisition rate. We developed a selective plane illumination microscopy endoscopic fiber platform, consisting of an ultrafast laser fabricated end-cap, integrated with a polymer coherent fiber bundle, and an epifluorescence microscope. Polymer fibers are known to fluoresce when pumped with blue light, enhancing the background and noise in images. Our end-cap design circumvents this challenge. We demonstrate a reduction of out-of-focus features, along with improved contrast of in-focus features, in images of a tissue phantom. Moreover, we demonstrate the utility of our platform for endomicroscopy using a whole, ex vivo human lung model.